Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

PET Biomarkers in Treatment Resistant Depression

This study has been terminated.
(Needed PET facility closed)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01031810
First received: December 12, 2009
Last updated: September 15, 2014
Last verified: October 2013
  Purpose

The primary objectives of the study are to test whether brain Mono Amine Oxidase-A (MAO-A) levels are elevated in patients with treatment-resistant major depression, and to explore whether MAO-A brain levels predict treatment outcome with Mono Amine Oxidase Inhibitor (MAOI) medication in this population.


Condition Intervention Phase
Major Depressive Disorder
Drug: tranylcypromine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Developing a Biomarker to Predict Response in Treatment Resistant Depression

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale Scores 17 at Baseline [ Time Frame: Week 00 (baseline) ] [ Designated as safety issue: No ]

    HAM-D is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Each item on the questionnaire is scored on a 3 or 5 point scale, depending on the item, and the total score is compared to the corresponding descriptor.

    Scale range (0-52):

    A score of 0-7 is considered to be normal. Scores of 20 or higher indicate moderate, severe, or very severe depression, and are usually required for entry into a clinical trial.


  • Hamilton Depression Rating Scale Scores 17 at week12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    HAM-D is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Each item on the questionnaire is scored on a 3 or 5 point scale, depending on the item, and the total score is compared to the corresponding descriptor.

    Scale range (0-52):

    A score of 0-7 is considered to be normal. Scores of 20 or higher indicate moderate, severe, or very severe depression, and are usually required for entry into a clinical trial.



Secondary Outcome Measures:
  • Quick Inventory of Depression- Self Report 16 [ Time Frame: Weeks 00 ] [ Designated as safety issue: No ]

    Quick Inventory of Depression- Self Report assesses 16 depressive symptoms experienced in the past week, based on self-rating, measured at study exit visit

    Scale range (0-27):

    Each of the four possible answers to each quiz is given an ascending numerical value from 0 to 3, and the total test score is the sum of the following: The highest number from questions 1-4 The number from question 5 The highest number from questions 6-9 The total of each question from 10-14 The highest number from questions 15-16

    Total score interpretation: 0-5 no depression, 6-10 mild depression, 11-15 moderate depression, 16-20 severe depression, 20 and above very severe depression


  • Quick Inventory of Depression- Self Report 16 [ Time Frame: Week 04 ] [ Designated as safety issue: No ]

    Quick Inventory of Depression- Self Report assesses 16 depressive symptoms experienced in the past week, based on self-rating, measured at study exit visit

    Scale range (0-27):

    Each of the four possible answers to each quiz is given an ascending numerical value from 0 to 3, and the total test score is the sum of the following: The highest number from questions 1-4 The number from question 5 The highest number from questions 6-9 The total of each question from 10-14 The highest number from questions 15-16

    Total score interpretation: 0-5 no depression, 6-10 mild depression, 11-15 moderate depression, 16-20 severe depression, 20 and above very severe depression


  • Quick Inventory of Depression- Self Report 16 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    Quick Inventory of Depression- Self Report assesses 16 depressive symptoms experienced in the past week, based on self-rating, measured at study exit visit

    Scale range (0-27):

    Each of the four possible answers to each quiz is given an ascending numerical value from 0 to 3, and the total test score is the sum of the following: The highest number from questions 1-4 The number from question 5 The highest number from questions 6-9 The total of each question from 10-14 The highest number from questions 15-16

    Total score interpretation: 0-5 no depression, 6-10 mild depression, 11-15 moderate depression, 16-20 severe depression, 20 and above very severe depression


  • Quick Inventory of Depression- Self Report 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]

    Quick Inventory of Depression- Self Report assesses 16 depressive symptoms experienced in the past week, based on self-rating, measured at study exit visit

    Scale range (0-27):

    Each of the four possible answers to each quiz is given an ascending numerical value from 0 to 3, and the total test score is the sum of the following: The highest number from questions 1-4 The number from question 5 The highest number from questions 6-9 The total of each question from 10-14 The highest number from questions 15-16

    Total score interpretation: 0-5 no depression, 6-10 mild depression, 11-15 moderate depression, 16-20 severe depression, 20 and above very severe depression



Enrollment: 13
Study Start Date: November 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
tranylcypromine
patients will receive treatment with tranylcypromine
Drug: tranylcypromine
MAO-Inhibitor 60mg-120mg
Other Name: Parnate

Detailed Description:

While Major Depressive Disorder (MDD) is prevalent and disabling, compelling recent data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study indicate that only about half of patients attain remission from MDD, even after multiple antidepressant medication trials. Further, no biomarker has been validated which can select an effective treatment for such patients, presenting critical unmet intellectual and clinical challenges. The recent landmark finding of an markedly elevated level of monoamine oxidase A (MAO-A) in the brains of depressed patients with MDD compared to controls, using positron emission tomography (PET) with a positron-emitting carbon isotope, (carbon 11 [11C]) labeled monoamine oxidase inhibitor (MAOI), has provided an unparalleled opportunity to address these challenges. It has long been known that MAOIs are effective for some patients with treatment-resistant MDD, although their side effect profile makes them highly unacceptable both to patients and physicians, severely curtailing their utility.

This study seeks to: 1) replicate this study using PET scans in 20 subjects with MDD but extending it to patients with treatment-resistant depression (TRD). (Results from these participants with be compared to those from 10 non-depressed controls; 2) explore the correlation of the brain MAO-A level biomarker to treatment outcome by treating the 20 PET-imaged TRD patients with an MAOI, hypothesizing that their MAOI response will be related to their level of MAO-A. Brain MAO-A is an ideal candidate biomarker for this study since it appears to be significantly abnormally elevated in MDD, yet it has a broad range of values even among depressed patients. Most importantly, the MAO-A biomarker is known to be the single pharmacologic target of the treatment, making it appear likely that outcome with MAOI treatment will be related to MAO-A.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

INCLUSION:

  1. Primary diagnosis of Major Depressive Disorder
  2. Subjects aged 18-65
  3. Depressed subjects must have Treatment-Resistant Depression (TRD) two previous adequate antidepressant treatment trial failures within the current depressive episode from different classes
  4. Minimum baseline Montgomery Asberg Depression Rating Scale (MADRS) score of 22
  5. Signs informed consent form
  6. Subjects must be willing to be have a PET scan
  7. Subjects must be antidepressant medication free for 3 weeks prior to PET scan

EXCLUSION

  1. Significant past or present neurological disorder, including seizures, stroke, or head trauma
  2. History of bipolar disorder, psychosis, schizoaffective disorder, or schizophrenia
  3. Moderate or high level of suicide risk, as determined by a score of 3 or 4 on item 3 of the HAM-D scale. Also excluded will be those who present a significant suicide risk by history or current psychiatrist's assessment.
  4. Personality disorder which might interfere with compliance or increase suicide risk
  5. Alcohol or drug abuse or dependence in the past year; history of lifetime IV drug use or use of methylene diamine methamphetamine (MDMA or "ecstasy") more than twice
  6. Current thyroid dysfunction (past or currently treated dysfunction is acceptable)
  7. Clinically significant or unstable medical conditions or laboratory abnormalities, including hypertension (repeated BP > 140 systolic, > 90 diastolic)
  8. Intake of investigational (unapproved) drug in the past 3 months
  9. Electroconvulsive therapy (ECT) in three months prior to screening
  10. Use of Vagal Nerve Stimulation (VNS)
  11. Positive drug of abuse screen
  12. Anticoagulant treatment which cannot be discontinued for 10 days prior to PET scanning
  13. Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months.
  14. Dementia (clinical and neurocognitive criteria)
  15. Claustrophobia of a severity which would not permit the participant to undergo an MRI or a PET scan
  16. Recent (< 7 days) consumption of Ayahuasca Tea or other South American non-standard decoction.
  17. Presence of metallic devices, implants and other contraindications to scanning
  18. Current, past or anticipated exposure to radiation, that may include being badged for radiation exposure in the workplace or participation in nuclear medicine research protocols
  19. Smokers (use of tobacco products in the previous 3 months)
  20. Potential participants having taken an antidepressant medication in the last 3 weeks. Participants otherwise eligible may elect to discontinue medication which has not been significantly helpful according to their report, their current psychiatrist's report (if available), and the evaluating psychiatrist. No patient will be asked to discontinue an effective antidepressant medication to participate.
  21. History of previous MAO-I treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01031810

Locations
United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Patrick J McGrath, MD New York State Psychiatric Institute, Columbia University
  More Information

Additional Information:
No publications provided

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01031810     History of Changes
Other Study ID Numbers: 6025, RC1MH088405-01
Study First Received: December 12, 2009
Results First Received: October 8, 2013
Last Updated: September 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York State Psychiatric Institute:
Treatment Resistant depression
Major Depression
MDD
Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mental Disorders
Mood Disorders
Tranylcypromine
Anti-Anxiety Agents
Antidepressive Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Monoamine Oxidase Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 25, 2014